Method for closing cartridges, supporting structure for supporting cartridge closures and transport or packaging container

ABSTRACT

In a method for closing a plurality of medical cartridges ( 5 ) a closure nest for supporting a plurality of closures is used, comprising a planar supporting plate having a plurality of receptacles having a plurality of tubular receptacles ( 61 ) and retaining structures for reliably accommodating the closures ( 200 ). In the method the plurality of medical cartridges ( 5 ) is supported in a corresponding cartridge nest. The closure nest is disposed above the cartridge nest so that the receptacles of the closure nest are precisely aligned with the receptacles of the cartridge nest. The closures ( 200 ) are then pushed downward out of the receptacles of the closure nest and into the cartridges ( 5 ), while the cartridges are supported by the cartridge nest. The closure nest can be directly fed on existing filling and stoppering machine set-ups for processing sealed prefillable syringe barrels, basically without the necessity of changing the set-up.

The present application claims priority of Indian patent application no.1590/MUM/2015, “A PRECRIMPED PRESTERILIZED CARTRIDGES NEST AND TUBASSEMBLY FOR FEEDING ON EXISTING PREFILLABLE SYRINGES MACHINES”, filedon 17 Apr. 2015, and of PCT-application no. PCTIN2015000394, “SUPPORTINGSTRUCTURE FOR SUPPORTING SEALED CARTRIDGES, TRANSPORT OR PACKAGINGCONTAINER AND PROCESS FOR PROCESSING THE SAME”, filed on 16 Oct. 2015,the whole content of which is hereby incorporated for reference.

FIELD OF INVENTION

The present invention relates in general to the processing of a batch ofsealed cartridges, particularly of pre-crimped cartridges, for use inpharmaceutical, medical or cosmetic applications and relates inparticular to a supporting structure (also named nest) provided forholding closures, such as elastic plugs or plunger stoppers, for use ina process for closing or stoppering cartridges. Further aspects of thepresent invention relate to a nest and tub assembly accommodating suchclosures, which can be directly fed on existing filling and stopperingmachine set-ups for processing sealed prefillable syringe barrels.Further aspects of the present invention relate to a stoppering processand to an integrated filling and stoppering process for processingsealed prefillable syringe barrels.

BACKGROUND OF INVENTION

Conventionally presterilized prefillable syringe barrels are supplied intub and nest assemblies that are hermetically sealed to the environmentto pharmaceutical customers, who then fill medicine into thepresterilized nested syringe barrels under sterile conditions usingfilling and stoppering machines. In the market there are three types offilling and stoppering machines available, namely 1) manual machines, 2)semi automatic machines and 3) fully automatic machines.

There is one tub and nest format available in the market for pre-crimpedcartridges but there are lots of disadvantages to use this existing tubeand nest format with existing as well as new filling and stopperingmachines because this tub and nest format requires complete settingchange from infeed to outfeed for accommodating different height levelof cartridge into the nest. Moreover a complete replacement of fillingcarriers is required for maintaining the height between the fillingnozzles and the cartridge top level. Further the drawback of twodifferent change parts needs separate validation study as per GMP (GoodManufacturing Practice) guidelines requirements. If one tries to fillthe pre-crimped cartridge nest available in the market on the samemachine without changing the machine height setting accidents willhappen which may cause damage to the filling nozzles or glass cartridgesmay get broken because the height difference between the filling nozzlesand the pre-crimped cartridges is too small.

These disadvantages similarly hold 1) for manual filling and stopperingmachines, which are operated electrically and pneumatically and wherethe processes are triggered by an operator, 2) for semi automaticfilling and stoppering machines, which are operated electrically,electronically and pneumatically and where the operator has to removethe outer bag of the tub and nest assembly and then a top lid from thetub along with an inner sheet, and 3) for fully automatic filling andstoppering machines, which are operated electrically, electronically andpneumatically and where whole packets are inserted into the filling andstoppering machine one by one, the machine will automatically remove theouter bag and then remove the top lid from the tub by means of anautomatic peeling off unit, then the inner sheet of the tub and nestassembly will be removed automatically and the machine will thenautomatically pick up the nests by means of a vacuum cup and place themonto transport carriers, which are then moved towards the fillingstation nozzles for the medicine filling process.

The currently available tub and nest assemblies in the market requirethe replacement of filling carriers for maintaining an accurate heightdifference between the filling nozzles and the cartridge top levels.Further after replacement of the filling carriers the replacement partsrequire separate validation studies as per GMP guidelines requirements.If the tub and nest assemblies available in the market are directly fedfor filling of pre-crimped cartridges on the same machine without anyalterations in the filling machines then the filling nozzles can bedamaged or glass cartridges can be broken because the height differencebetween the filling nozzles and the pre-crimped cartridges is too small.All the above activities will incur higher costs and also additionaltime will be required to change the parts resulting in productionlosses. Further all fully automatic machines and new separate changeparts are very expensive.

The above drawbacks are overcome by a supporting structure forsupporting a plurality of sealed cartridges for use in pharmaceutical,medical or cosmetic applications, by a transport or packaging containeraccommodating such a supporting structure and by a process forprocessing a batch of sealed cartridges using such a supportingstructure as disclosed in Indian patent application no. 1590/MUM/2015and PCT-application no. PCTIN2015000394 of the Applicant, the wholecontent of which is hereby incorporated for reference.

US 2013/0161225 A1 discloses a packaging unit for the transport andprocessing of syringe bodies, comprising a tray which can retain aplurality of syringe bodies in a suspended vertical position, and acover which can cover the tray. The cover comprises at least two flankswhich can embrace the tray. According to an embodiment openings areprovided in the upper wall of the cover which permit the circulation ofsteam or gas during a sterilization process. According to a furtherembodiment, these openings are placed above openings in the containers,and thus permit filling and/or plugging of the containers.

Conventionally, cartridges are closed by feeding closures, such aselastic plugs or plunger stoppers, individually to a closing machine andclosing the cartridges individually, as disclosed e.g. in US2014/0069062 A1. This often requires removal of the cartridges from acarrier after filling and re-inserting the cartridges after closing intothe carrier again, as disclosed e.g. in U.S. Pat. No. 8,978,344 B2.

Typically the closures are singulated using vibratory bowls andtransported using vibratory chutes. The vibratory bowl and chutescontact the stoppers, the surfaces of which will eventually be in directcontact with the product inside the container. To address this problem,it is generally considered necessary to steam sterilize the vibratorybowls and chutes. However, is practically impossible to transfer thestopper bowl and chutes aseptically from the sterilizing autoclave tothe processing environment.

US 2012/0248057 A1 discloses a capping system method for sealingpharmaceutical vials. A plurality of vials are disposed upright in atub, which also accommodates a respective closure assembly for each vialcomprising a preassembled elastomeric stopper and a retainer member.Each closure member is placed on the neck of its associated vial so thata portion of the stopper partially closes the opening of the vial.Thereafter a force is applied to each of the closure assemblies to causethe retainer members to snap-fit on the flanged neck of their associatedvial so that portions of their associated stopper seal the opening intheir associated vial. This approach makes it easier to seal the vialsunder aseptic conditions.

A process for filling pharmaceutical containers that uses a similarcapping system is disclosed in WO 2015/023924 A2. The process uses neststhat are configured to allow multiple closures and containers to besimultaneously aligned concentrically, and closed simultaneously.Spring-loaded retaining structures on the closure nest allow it toreleasably retain multiple closures above the corresponding multiplecontainers. The retaining structures used are, however, stillcomplicated and it is not easy to use this approach in the existingmachinery of pharmaceutical fillers.

SUMMARY OF INVENTION

According to the present invention there is provided a stopperingprocess or an integrated filling and stoppering process for processingsealed prefillable syringe barrels using a supporting structure forholding a plurality of closures. According to a further related aspectof the present invention there is provided a supporting structure forholding a plurality of closures (nest for closures), such as elasticplugs or plunger stoppers, for use in the process for closing orstoppering cartridges. According to a related further aspect of thepresent invention there is provided a transport or packaging container(nest and tub assembly) accommodating at least one nest for closuresconfigured so that the nest accommodating the closures can be directlyfed on existing filling and stoppering machine set-ups for processingsealed prefillable syringe barrels.

A supporting structure for closures according to the present invention,for use in the stoppering process or an integrated filling andstoppering process, is configured for releasably supporting a pluralityof closures, which have a cylindrical shape, consist of a resilientmaterial and are for use for closing cartridges for use inpharmaceutical, medical or cosmetic applications. The supportingstructure for closures comprises a planar supporting plate having aplurality of tubular receptacles for accommodating the closures at leastpartially, for concurrently supporting a plurality of closures at thesupporting plate. According to the present invention the receptacles areformed by circumferential side walls disposed in a regular arrangementat the supporting plate and protruding from the supporting plate,wherein the receptacles are configured for accommodating the closures atleast partially.

The supporting structure for closures allows to releasably hold aplurality of closures exactly in the same two-dimensional arrangement asa supporting structure for cartridges disclosed in Indian patentapplication no. 1590/MUM/2015 and PCT-application no. PCTIN2015000394 ofthe Applicant. This simplifies a process for closing the cartridgessignificantly, because this process only requires disposing thesupporting structure for closures above the supporting structure forcartridges in an environment with reduced pressure so that thereceptacles of the supporting structure for closures are aligned withtheir associated receptacles of the supporting structure for cartridges,and pushing the closures downward out of the receptacles of thesupporting structure for closures and into the filling openings at theupper ends of the cartridges while the cartridges are accommodated inthe receptacles of the supporting structure for cartridges.

As the supporting structure according to the present invention can beeasily accommodated and stored or transported in a transport container(tub), the present invention enables using the existing tube and nestformat widely used in the market with existing as well as new fillingand stoppering machines. Furthermore, the supporting structure accordingto the present invention can be used to efficiently store and supply aplurality of closures in a predetermined geometrical arrangement understerile conditions, using the tube and nest format widely used in themarket.

The receptacles may accommodate the closures fully or only partially,depending on the circumstances of the further processing of the closuresand cartridges. The supporting plate is preferably made of a plasticmaterial, e.g. by plastic injection molding, and offers sufficientstrength, stiffness and mechanical stability, although theserequirements are usually easy to fulfill, because the closures to beaccommodated are light-weight and only small forces are usually exertedon the supporting plate during further processing.

The closures may be accommodated in the receptacles solely by friction.As the closures are made of an elastic, resilient material, insertingthe closures into the receptacles might involve imposing a slightelastic deformation of the closures so that the closures abutresiliently against the circumferential side walls of the receptacles.As the closures are light-weight, a reliably accommodation of theclosures would usually require only a small degree of deformation of theclosures, which corresponds to small forces required only for insertingor removing the closures into and out of the receptacles. As closuresfor cartridges, such as plunger stoppers, usually have several annularbulges on their outer circumference, this slight elastic deformationwould usually occur only in the region of these annular bulges. Thus,the side walls of the receptacles are preferably straight side-wallsdefining cylindrical receptacles that are not tapered.

For more reliably accommodating the closures in the receptacles,according to a further embodiment the receptacles comprise retainingstructures that releasably engage with the closures for retaining theclosures in the receptacles. Preferably the retaining structures engagewith the closures in a form-fitting manner. This form-fitting engagementmay be implemented at the upper and bottom ends of the closures, or atany other suitable positions, such as at the bottom ends and at centralportions of the closures, which might be concavely curved for example inthe case of plunger stoppers. For this purpose, the retaining structuremay slightly protrude into the interior of the receptacles to retain theclosures.

According to a further embodiment the protrusions are formed on theinner sides of the circumferential side walls of the receptacles, whichmay be easily accomplished by integrally forming the protrusions withthe side-walls of the receptacles, e.g. by plastic injection molding.

According to a further embodiment the protrusions may be configured tomate to the outer contour of the closures. If e.g. the outer contour ofthe closures is undulated, the protrusions may at least be partiallyundulated in correspondence to the outer contour of the closures.

According to a further embodiment the protrusions may be formed at equalangular distances along the inner sides of the circumferential sidewalls of the receptacles, e.g. as small spot-like protrusions. Accordingto an alternative embodiment, however, the protrusions may also beformed as circumferential protrusions on the inner sides of thecircumferential side walls of the receptacles.

According to a further embodiment the receptacles may comprise upperretaining structures formed at or near an upper end of the receptaclesand bottom retaining structures formed at a bottom end of thereceptacles, wherein the distance between the respective upper andbottom retaining structures may be equal to the axial length of theclosures so that the closures are reliably fixed in both axialdirections in the receptacles. The closures may even rest on theseretaining structures thus enabling a substantially frictionlessaccommodation of the closures in the receptacles and removing theclosures out of the receptacles with small forces only. According to afurther embodiment, however, this distance may also be smaller, e.g. ifone of the retaining structures engages with a portions of the closuresin a form-fitting manner.

According to a particularly preferred embodiment the upper retainingstructures may be formed as convexly curved protrusions protruding fromthe inner sides of the circumferential side walls of the receptacleswhich enables an insertion of the closures into the receptacles withsmall forces and a slight elastic deformation only, whereas the bottomretaining structures may be formed as hook-like protrusions protrudingfrom the inner sides of the circumferential side walls of thereceptacles, which enables to push down the closures out of thereceptacles simultaneously because the timing when the retaining forcesare overcome by a pushing force of a stoppering machine can be preciselyadjusted, e.g. by means of the geometric shape of the bottom retainingstructures, their material and strength.

According to a particularly preferred embodiment the bottom retainingstructures may beveled on an upper and/or lower side thereof. While thebevel on the upper side eases the pushing down of the closures out ofthe receptacles during a stoppering process, the bevel on the lower sidemay helpful if the receptacles are directly supported on upper ends ofthe cartridges during the stoppering process, because the bevels on thelower sides may then snuggle to these upper ends and peak forces ortension may thus be avoided, particularly if the bottom retainingstructures are made of a resilient plastic material.

According to a further related aspect of the present invention there isprovided a transport or packaging container for accommodating aplurality of closures for closing cartridges for use in pharmaceutical,medical or cosmetic applications, wherein the transport or packagingcontainer is box-shaped and comprises: a bottom, which is closed orsealed by a seal, upstanding lower side-walls extending essentiallyperpendicularly from said bottom, a circumferential supporting stepextending horizontally from said side-walls, upper side-walls extendingupward from said supporting step, and a circumferential flange formed atupper ends of the upper side-walls. According to the present inventionat least one supporting structure for closures as disclosed in thepresent application is accommodated in the transport or packagingcontainer, wherein the plurality of closures are accommodated in thereceptacles of the at least one supporting structure for closures.

The transport or packaging container for closures enables the storageand transport of a plurality of closures in exactly the same format asthe existing tube and nest format widely used in the market so that itmay be used easily with existing as well as new filling and stopperingmachines without the necessity of changing the whole setup thereof.

According to a further embodiment the edge of the bottommost planarsupporting plate of the supporting structure for closures may besupported directly on the circumferential supporting step or thetransport or packaging container.

According to a further embodiment a plurality of supporting structuresfor closures may be accommodated together inside the transport orpackaging container stacked one above the other. For this purpose,spacers might be provided on the bottom sides of the supporting plates.However, this is usually not required, because usually the bottom endsof the receptacles of an upper closure nest may rest directly on thebottom surface of another closure nest, because the outer diameter ofthe receptacles is larger than the inner diameter of the receptacles, sothat the receptacles of the upper closure nest cannot enter thereceptacles of another closure nest. For this purpose, it might be ofadvantage if the upper ends of the closures are disposed at a certainminimum distance to the upper ends of the receptacles.

According to a further embodiment the transport or packaging containeris closed or sealed by a protective foil against the environment, theprotective foil being bonded to the circumferential flange. Theprotective foil may be impermeable to gas, thus implementing completelysterile conditions during storage and transport of the closures.

According to a particularly preferred embodiment the protective foil maybe a gas-permeable plastic film enabling a sterilization of the interiorof the transport or packaging container through the protective foil by aflow of a sterilization gas, such as ethylene oxide. Particularly theprotective foil may be made of a web of synthetic fibers such aspolypropylene fibers (PP) or a Tyvek® protective film for this purpose.

According to a further related aspect of the present invention there isprovided a method for closing a plurality of cartridges for use inpharmaceutical, medical or cosmetic applications, said cartridges havingan upper end and a bottom end opposite to the upper end, a cylindricalbody of a first outer diameter with a filling opening at the upper end,and a shoulder portion at the bottom end with a secondary opening whichis sealed by a seal, a predetermined axial length being defined betweenthe upper end and the bottom end, said method comprising: providing asupporting structure for closures as disclosed in the presentapplication accommodating a plurality of closures in the receptacles ina regular arrangement; providing a supporting structure for cartridgesas disclosed in Indian patent application no. 1590/MUM/2015 andPCT-application no. PCTIN2015000394 of the Applicant, accommodating aplurality of cartridges in the same regular arrangement as in thesupporting structure for closures; disposing the supporting structurefor closures above the supporting structure for cartridges in anenvironment with reduced pressure so that the receptacles of thesupporting structure for closures are aligned with the receptacles ofthe supporting structure for cartridges; and pushing the closuressimultaneously downward out of the receptacles of the supportingstructure for closures and into the filling openings at the upper endsof the cartridges while the cartridges are accommodated in thereceptacles of the supporting structure for cartridges.

The nest accommodating the closures can be directly fed on existingfilling and stoppering machine set-ups for processing sealed prefillablesyringe barrels. The method according to the present invention can beimplemented easily for cartridges of different lengths, because thisrequires just an adjustment of the distance between the supportingstructure for closures and the supporting structure for cartridges,which can be accomplished by a simple vertical adjustment of eithersupporting structure, which does not change the exact alignment of thereceptacles of both supporting structures.

According to a further embodiment the supporting structure forcartridges is held by a bottom holding frame, whereas the supportingstructure for closures is held by an upper holding frame, wherein thebottom holding frame and the upper holding frame are disposed at a fixedspacing and aligned with each other by alignment devices. For thispurpose one of the holding frames may be provided with alignmentdevices, such as protrusions, rods or the like, that cooperate withcorresponding alignment devices, such as holes or recesses, provided onthe other holding frame. Thus, an exact, reliable alignment of allreceptacles of the supporting structures can be accomplished easily.

According to a further embodiment the upper holding frame may bedisposed at such a distance to the bottom holding frame that bottom endsof the receptacles of the upper holding frame or bottom ends of thereceptacles of the supporting structure for closures held by the upperholding frame are in direct contact with the upper ends of thecartridges accommodated in the receptacles of the supporting structurefor cartridges so that the closures are directly guided into the openupper ends of the cartridges if pushed down out of the receptacles ofthe supporting structure for closures.

In this method, the supporting structures for closures and/or thesupporting structures for cartridges may be supplied under sterileconditions, e.g. to a pharmaceutical filler, in transport and packagingcontainers as outlined in the following in more detail.

Of course, the method according to the present invention may involveadditional processing steps, particularly a step of filling theplurality of cartridges with a pharmaceutical, medical or cosmeticproduct, which can be performed in any suitable sequence, particularlyrow-wise or simultaneously for all cartridges supported by a supportingstructure.

According to a further embodiment this step of filling the plurality ofcartridges with the pharmaceutical, medical or cosmetic product may beperformed while the supporting structure for cartridges is held in thesame bottom holding frame used during stoppering.

The above aspects of the present invention are thus closely related to asupporting structure for supporting a plurality of sealed cartridges foruse in pharmaceutical, medical or cosmetic applications as disclosed inIndian patent application no. 1590/MUM/2015 and PCT-application no.PCTIN2015000394 of the Applicant, said cartridges having an upper endand a bottom end opposite to the upper end, a cylindrical body of afirst outer diameter with a filling opening at the upper end, and ashoulder portion at the bottom end with a secondary opening which issealed by a seal, a predetermined axial length being defined between theupper end and the bottom end. The supporting structure comprises aplanar supporting plate, and a plurality of tubular receptacles formedat the planar supporting plate in a regular arrangement and extendingdownward from a bottom side of the planar supporting plate foraccommodating the sealed cartridges, wherein retaining protrusions areformed at the bottom ends of the receptacles protruding inward, and theaxial length of the receptacles is smaller than the axial length of thesealed cartridges.

According to the present invention the retaining protrusions are matedwith the shoulder portions of the sealed cartridges in such a mannerthat the shoulder portions of the sealed cartridges are supported on theretaining protrusions of the receptacles and that the upper ends of thesealed cartridges protrude from the upper ends of the receptacles at anupper side of the planar supporting plate, when the sealed cartridgesare accommodated upside-down in the receptacles.

Because the seals of the cartridges at their bottom ends, which aresusceptible to damage upon application of excessive forces, do not reston a supporting surface the cartridges, once filled, may be stoppered(closed at their upper ends with rubber plugs, plungers or similarsealing members) without damaging the seals at the bottom ends. At thesame time, the filling openings, which extend beyond the upper rims ofthe receptacles, are freely accessible for processing.

According to a further embodiment the receptacles are of cylindricalshape and a plurality of ribs are formed at equidistant angular spacingon inner circumferential side-walls of the receptacles, preferably atdiametrally opposite positions thereof, wherein the ribs protruderadially inward from the inner circumferential side-walls of thereceptacles for centering the sealed cartridges inside the receptacles.Thus, a reliable centering of the cartridges, a rattle-free storageinside the receptacles and a smooth, rattle-free insertion into andremoval out of the receptacles may be accomplished. Further, forcesexerted e.g. upon stoppering may be distributed more efficiently withoutdeformation of the receptacles, thus ensuring a more precise centeringand positioning of the cartridges inside the receptacles.

According to a further embodiment the retaining protrusions are formedas ring segments that protrude radially inward at the bottom ends of thereceptacles and at equidistant angular spacing, preferably atdiametrally opposite positions thereof, thus enabling a more uniformdistribution of forces, particularly upon stoppering.

According to a further embodiment an outer diameter of the sealedcartridges at their sealed bottom ends is larger than the outer diameterat their shoulder portions but smaller than the first outer diameter.Further the thickness of the retaining protrusions in the axialdirection may be smaller than the axial length of the sealed bottom endsso that the sealed bottom ends of the sealed cartridges extend throughopenings formed by the retaining protrusions at the bottom ends of thereceptacles. The sealed bottom ends of the cartridges thus do not reston any supporting surfaces but hang free in space, thereby reducing therisk of mechanical damage upon stoppering and related processing steps.

According to a further embodiment the supporting plate is formed of aplastic material and the side-walls of the receptacles and the retainingprotrusions are formed unitary with the supporting plate, wherein theretaining protrusions are configured to sustain axial forces exertedonto the sealed cartridges of up to 1,000 N, preferably of up to 750 Nand more preferably of up to 500 N.

According to a further embodiment the front ends of the retainingprotrusions are wedge-shaped in correspondence with the outer contour ofthe shoulder portions of the sealed cartridges, thus enabling a morereliable and precise supporting of the shoulder portions and even lessdeformation of the retaining protrusions upon stoppering or relatedprocessing steps.

According to a further embodiment virtual connecting lines between thecenters of directly adjacent receptacles respectively form a hexagonwith a further receptacle disposed at a center of the respectivehexagon, wherein the receptacles extend beyond the upper surface of thesupporting plate and stiffening ribs protruding upward from the uppersurface of the supporting plate are formed on the upper surface of thesupporting plate so as to connect the circumferential side walls of thereceptacles, for stiffening the supporting plate. Thus, a ratherefficient stiffening of the supporting plate may be accomplished.

According to a further aspect of the present invention there is provideda transport or packaging container (tub) for accommodating a pluralityof sealed cartridges for use in pharmaceutical, medical or cosmeticapplications, wherein the transport or packaging container is box-shapedand comprises a bottom, which is closed or sealed by a seal, upstandinglower side-walls extending essentially perpendicularly from said bottom,a circumferential supporting step extending horizontally from saidside-walls, upper side-walls extending upward from said supporting stepand a circumferential flange formed at upper ends of the side-walls. Asupporting structure (nest) as disclosed hereinafter in more detail isaccommodated in the transport or packaging container and supports aplurality of sealed cartridges in the receptacles thereof. The nestrests directly on the supporting step of the tub. Thus, regardless ofwhether the cartridges are processed while being accommodated only inthe nest or in a tub and nest assembly it can be ensured that the upperends of all cartridges are on the same height level. Thus, a precisedistance between the upper ends of the cartridges and the bottom ends offilling nozzles or the like can be ensured reliably, thus avoidingbreakage or damage during processing of the cartridges.

According to a further embodiment the transport or packaging containerfurther comprises a flexible lid sealed onto the circumferential flangeof the transport or packaging container for sealing the transport orpackaging container, preferably for hermetically sealing the innervolume of the transport or packaging container against the environment.

According to a further aspect of the present invention there is provideda process for processing a batch of sealed cartridges for use inpharmaceutical, medical or cosmetic applications, comprising the stepsof: a) providing a supporting structure as disclosed hereinafter in moredetail; b) disposing the sealed cartridges upside-down in thereceptacles and with their upper ends protruding from the upper ends ofthe receptacles at an upper side of the planar supporting plate so thatthe shoulder portions of the sealed cartridges are supported on theretaining protrusions of the receptacles and the upper ends of thesealed cartridges are disposed at the same height level; c) feeding thesupporting structure with the sealed cartridges to a processing station;and d) processing the sealed cartridges at their upper ends at theprocessing station while being supported by the supporting structure.

According to a further embodiment step d) comprises one or more of thefollowing: filling the sealed cartridges via the filling openings at theupper ends; stoppering the sealed cartridges at their upper ends usingrubber stoppers; pre gassing and post gassing.

According to a further embodiment the process further comprises:disposing the supporting structure in a frame-like holding table;feeding the supporting structure together with the sealed cartridges tothe processing station while being supported by the frame-like holdingtable; and disposing the supporting structure with the sealed cartridgesinside a box-shaped transport or packaging container after said step d),which comprises a bottom, upstanding lower side-walls extendingessentially perpendicularly from said bottom, a circumferentialsupporting step extending horizontally from said side-walls, upperside-walls extending upward from said supporting step and acircumferential flange formed at upper ends of the side-walls so thatthe edge of the planar supporting plate of the supporting structure issupported on the circumferential supporting step of the transport orpackaging container, the upper ends of the sealed cartridges do notprotrude beyond the circumferential flange of the transport or packagingcontainer, and the bottom ends of the sealed cartridges are disposedspaced apart from the bottom of the transport or packaging container.

According to a further embodiment the process further comprises:disposing the supporting structure with the sealed cartridges inside abox-shaped transport or packaging container, which comprises a bottom,upstanding lower side-walls extending essentially perpendicularly fromsaid bottom, a circumferential supporting step extending horizontallyfrom said side-walls, upper side-walls extending upward from saidsupporting step and a circumferential flange formed at upper ends of theside-walls so that the edge of the planar supporting plate of thesupporting structure is supported on the circumferential supportingstep, the upper ends of the sealed cartridges do not protrude beyond thecircumferential flange of the transport or packaging container, and thebottom ends of the sealed cartridges are disposed spaced apart from thebottom of the transport or packaging container; wherein step c) furthercomprises: disposing the transport or packaging container in aframe-like holding table so that the supporting step of the transport orpackaging container is supported on an upper side of the frame-likeholding table and that the upper ends of the sealed cartridges aredisposed at the same height level; and feeding the frame-like holdingtable together with the transport or packaging container, the supportingstructure accommodated therein and the sealed cartridges to theprocessing station.

According to a further embodiment the transport or packaging containeris sealed with a flexible lid.

According to a further embodiment of the process the sealed cartridgesare pre-crimped cartridges.

OVERVIEW ON DRAWINGS

Hereinafter, the present invention will be disclosed in exemplary mannerand with reference to the drawings, wherein:

FIG. 1 is a perspective top view of a supporting structure forcartridges for use in a method according to the present invention;

FIG. 2 is a top view of the supporting structure of FIG. 1;

FIG. 3 is a bottom view of the supporting structure of FIG. 1;

FIG. 4 is a perspective bottom view of the supporting structure of FIG.1;

FIG. 5 is a schematic cross-section of the supporting structure of FIG.1 without cartridges;

FIG. 6a is an enlarged partial view from FIG. 5 showing how thecartridges are supported inside the receptacles of the supportingstructure according to the present invention;

FIG. 6b is a sectional view of a cartridge shown in FIG. 6 a;

FIG. 7 is an exploded view showing a transport or packaging containertogether with the supporting structure of FIG. 1 (tub and nest assemblyfor cartridges) with cartridges inserted into the receptacles of thesupporting structure and with one cartridge sealed at a bottom endthereof;

FIG. 8 is an enlarged partial view of the tub and nest assembly forcartridges of FIG. 7;

FIG. 9 shows the tub and nest assembly for cartridges of FIG. 7 with thesupporting structure for cartridges inserted and a sealing lid sealed onan upper edge of the transport or packaging container;

FIG. 10 is a schematic top view of a processing station for processingsealed cartridges using the supporting structure for cartridges in afilling process;

FIG. 11 is a schematic cross-sectional view of the tub and nest assemblyat a filling station used in a process according to the presentinvention;

FIGS. 12a-12c show details of a supporting structure for closures forcartridges according to a first embodiment of the present invention;

FIGS. 12d-12e show the accommodation of closures in the receptacles of asupporting structure for closures for cartridges according to a furtherembodiment of the present invention;

FIGS. 13a-13d show a transport or packaging container together with thesupporting structure of FIG. 12a (tub and nest assembly for closures)for accommodating a plurality of closures for cartridges, at variousstages of providing the transport or packaging container for closures;

FIGS. 14a-14h show a setup for simultaneously closing (stoppering) aplurality of cartridges using a nest for closures and a nest forcartridges with their receptacles in alignment at various stages;

FIG. 14g shows this setup in a perspective exploded view; and

FIG. 15 shows a method according to the present invention forsimultaneously closing (stoppering) a plurality of cartridges in aschematic sectional side view.

Throughout the drawings, the same reference numerals designate identicalor substantially the same components or groups of components.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

A supporting structure (in the following nest for cartridges orcartridge nest) in the sense of the present invention and as disclosedin Indian patent application no. 1590/MUM/2015 and PCT-application no.PCTIN2015000394 of the Applicant is used for concurrently supporting aplurality of sealed cartridges for use in pharmaceutical, medical orcosmetic applications. Such cartridges, including pen cartridges,by-pass cartridges and dental cartridges, are a commonly-used packagingsolution for drug delivery systems, e.g. insulin administration, pensystems, pump systems, auto-injectors and needle free injectors. Forspecial requirements such as by-pass and chemically strengthenedcartridges, personalized designs are available on the market. Cartridgesavailable on the market may be made of glass material, particularly ofFiolax® glass from SCHOTT AG, and offer fixed volumes for drug deliveryof e.g. 1.0 ml, 1.5 ml and 3.0 ml. Different volumes usually correspondto different axial lengths of the cartridges.

An example for such a cartridge embodied as a syringe barrel is shown inFIG. 6b and comprises an upper end with a filling opening 53, a bottomend 52 opposite to the upper end and a cylindrical body 50 of a firstouter diameter, which is usually identical with the diameter of thefilling opening 53 at the upper end of the syringe barrel. Thecylindrical body 50 merges into a tapered shoulder portion 51 at thebottom end of a reduced diameter, which is followed by widened bottomrim 52 with a secondary opening 54 used for drug administering. Afterfilling the cylindrical body 50, the filling opening 53 is closed bymeans of an elastomeric closure provided with or without a fluoropolymerbarrier coating, such as a thick rubber or plastic plug, which lateracts as a piston when the content is pressed out for drug administering.The secondary opening 54 is sealed by a seal, usually with a rubber plugwith septum (puncture rubber) provided with or without a fluoropolymerbarrier coating or with a combiseal. For protecting the septum andfixing the plug an outer closure (beaded cap or cramp), often made froman aluminum sheet or aluminum/plastic compound material, is used, whichis usually crimped over the widened bottom rim 52 to thereby tightlysecure the seal at the cartridge and thereby form a pre-crimpedcartridge in the sense of the present application. In thecross-sectional view of FIG. 6b such a pre-crimped cartridge including aseal 55 of the type mentioned above is shown on the right-hand andleft-hand side of the drawing, whereas the central cartridge is shown ina cross-section and without such a seal. As can be concluded from FIG.6b , a predetermined axial length is defined between the upper end andthe bottom end of the cartridge. Particularly, cartridges in the senseof the present invention do not have hand rests at their upper ends asconventional syringe bodies, and, if they would have such fingers rests,these hand rests would not be supported directly on a supporting plateor on members thereof, as outlined in more detail in the following, whensuch cartridges were accommodated in a nest.

Referring to FIGS. 1 to 4, a supporting structure for cartridges (in thefollowing nest for cartridges or cartridge nest) comprises a planarsupporting plate 10 having a plurality of tubular receptacles 11disposed in a regular arrangement, which at least extend downward fromthe bottom side of the planar supporting plate 11 (see bottom view ofFIG. 4), and preferably also protrude upward from the upper side of thesupporting plate, as shown in the perspective top view of FIG. 1. Thus,the tubular receptacles 11 are formed by the circumferential side-walls12, 14 protruding from the upper and bottom side of the supporting plate10, respectively. Preferably these side-walls 12, 14 are of cylindricalshape for accommodating the cartridges, although other shapes, such aspolygonal shapes are also possible. These receptacles 11 are disposed ina regular two-dimensional arrangement, at equidistant spacing. As shownin the top view of FIG. 2, virtual connecting lines between the centersof directly adjacent receptacles 11 respectively may form a hexagon witha further receptacle 11 disposed at a center of the respective hexagon.According to other embodiments, the receptacles may also be disposed atequidistant spacing along two mutually orthogonal directions.

The inner diameter of the receptacles is slightly larger than the outerdiameter of the cartridges to be accommodated. For enabling a precisecentering of the cartridges, a plurality of ribs 13 is formed on theinner circumferential surfaces of the side-walls 12, 14 protrudingradially inward. These ribs 13 are formed at equidistant angular spacingon the inner surfaces of the side-walls 12, 14, preferably atdiametrally opposite positions thereof, so that the total number ofthese ribs 13 may be e.g. equal to four or eight.

The upper ends of these ribs 13 preferably do not extend up to the upperrim of the side-walls 12. In order to enable a smooth insertion of thecartridges into the receptacles 11, the upper ends of the ribs 13 arepreferably slanted radially inward to guide the cartridges uponinsertion. Together, the ribs 13 span an inner volume of a diameter,which essentially equals the outer diameter of the cartridges, thusenabling an essentially rattle-free storage of the cartridges and asmooth, rattle-free axial movement of the cartridges upon insertion intoor removal out of the receptacles 11. The ribs 13 enable a precisecentering of the cartridges at predetermined positions, so thatautomated processing systems may expect the cartridges at preciselypredetermined positions upon their transfer to a processing station,which significantly reduces the efforts required for automation.

As shown in FIG. 6a , the axial length of the receptacles 11 is smallerthan the axial length of the cartridges to be accommodated, so that inuse the upper ends with the filling openings 53 extend beyond the upperrim of the upper side-walls 12 of the receptacles so that the fillingopenings 53 are freely accessible for processing, e.g. for performing afilling operation as shown in FIG. 11.

As shown in FIGS. 4 to 6, retaining protrusions 15 are formed at thebottom ends of the receptacles 11 protruding radially inward. Theseretaining protrusions 15 are mated with the shoulder portions 51 of thecartridges in such a manner that the shoulder portions 51 are directlysupported on the retaining protrusions 15 of the receptacles 11 when thecartridges are accommodated upside-down in the receptacles 11, as shownin FIG. 6. Furthermore, the axial length of the receptacles is matedsuch to that of the cartridges that the upper ends of the cartridgesprotrude from the upper ends of the receptacles 11, as shown in FIG. 6.

As shown in FIGS. 3 and 4, the retaining protrusions 15 are formed asring segments that protrude radially inward at the bottom ends of thereceptacles 11 and at equidistant angular spacing, preferably atdiametrally opposite positions. As shown in FIG. 3, gaps 16 ofessentially rectangular profile are formed between adjacent ones of theretaining protrusions 15. These gaps 16 preferably extend up to theinner surface of the side-walls 14 of the receptacles 11. Theafore-mentioned axial ribs 13 may extend downward to the retainingprotrusions 15, but for a precise centering of the cartridges this isnot essential.

For a smooth and more stable and precise supporting of the cartridges,the front ends of the retaining protrusions 15 may be slanted orwedge-shaped in correspondence with the outer contour of the shoulderportions 51 of the cartridges to be accommodated.

As shown in FIG. 6b , the outer diameter of the sealed or pre-crimpedcartridges 5 at their sealed bottom ends is larger than the outerdiameter at their shoulder portions 51 but smaller than the (first)outer diameter of the cylindrical body 50. Further, the thickness of theretaining protrusions 15 in axial direction is smaller than the axiallength of the sealed bottom ends of the sealed cartridges 5 so that thesealed bottom ends of the sealed cartridges extend through centralopenings 17 (shown in FIG. 5) formed by the retaining protrusions 15 atthe bottom ends of the receptacles 11.

The supporting plate 10 of a nest 1 according to the present inventionis preferably formed of a plastic material and the side-walls 12, 14 ofthe receptacles 11 and the retaining protrusions 15 are thus formedunitary with the supporting plate 10. For enabling a stoppering of thefilling openings 53 with rubber plugs or syringe plungers while thecartridges are accommodated in the receptacles 11 of the nest 1, theretaining protrusions 15 are preferably configured to sustain typicalaxial forces exerted onto the sealed cartridges upon stoppering of up to500 N, preferably of up to 750 N and more preferably of up to 1,000 N,which can be ensured easily by a suitable choice of the plastic materialand material strength of the supporting plate 10 and all its members.

As shown in FIGS. 2 and 4, for stiffening the supporting plate 10,stiffening ribs 26, 28 may be provided on the upper side and bottomside, respectively, of the supporting plate 10, connecting the upperside-walls 12 and bottom side-walls 14 of the receptacles. In thearrangement of the receptacles 11 shown in FIG. 2, these stiffening ribs26 thus form hexagons interconnecting directly adjacent ones of thereceptacles and triangles connecting the outer ones of these receptacleswith a further receptacle 11 disposed in the center of a respectivehexagon. As shown in FIG. 4, these stiffening ribs ribs 28 mayinterconnect the side-walls 14 of the outer ones of the receptacles 11.Furthermore, central stiffening 28 may also be provided near the centerof the supporting plate 10, for interconnecting central ones of thesereceptacles 11. In a preferred embodiment, such a nest 1 will be made ofa plastic material using plastic injection-molding techniques. Despitethe afore-mentioned stiffening measures, the supporting plate 10 maystill be flexible to a certain extent, if required.

For the transport, storage and packaging of a nest 1 as outlined abovetogether with the cartridges accommodated therein a transport orpackaging container 3 (hereinafter also named tub for cartridges) isused as schematically shown in FIG. 7. According to FIG. 7, thetransport or packaging container 3 is essentially box-shaped ortub-shaped and has a base 30, a circumferential side wall 31 protrudingessentially in vertical direction therefrom, a supporting step 32protruding essentially rectangular therefrom, a circumferential upperside wall 33 and an upper rim 34 which is formed as a flange. Thecorners 35 of the transport or packaging container 3 are suitably formedrounded, particularly near the supporting step 32. Preferably, the upperside wall 33 is formed inclined at a small angle of inclination withrespect to a vertical to the base 30 in order to ease the insertion ofthe nest 1. Such a transport or packaging container 3 is preferablyformed from a plastics material, particularly by plastic injectionmolding, and is preferably formed of a clear transparent plastic inorder to enable a visual inspection of the nest 1 accommodated in thetransport or packaging container 3 and of the cartridges 5 supported byit.

In this manner, the nest 1 can be positioned precisely in the transportor packaging container 3 and thus the plurality of cartridges 5 can bepositioned and held in a regular array and at precisely definedpositions in a transport or packaging container 3 with standardizeddimensions. In particular, it can be ensured in this way that allbottoms or bottom ends of the cartridges are positioned in a planedefined jointly and in parallel to the base 30 and that all upper endsare positioned in a plane defined jointly and parallel to the upper rim34 of the transport or packaging container 3. As shown in FIG. 9, theupper ends of the cartridges do not extend beyond the upper rim 34 ofthe transport or packaging container 3 but are spaced apart to the upperrim 34.

As shown in FIG. 9 a packaging unit (also named tub and nest assembly)formed by the transport or packaging container (tub) 3 and the nest 1with the cartridges 5 accommodated therein is closed or sealed at leaston the upper side by means of a protective foil or packaging foil 6bonded onto the upper flange-like edge 34 of the tub 3. Thus, it isensured that the interior of tub 3 is hermetically sealed from theenvironment, from manufacture until the time when access is to be gainedto the interior of the tub 3 for further processing of the cartridges 5.The protective foil 6 may be in particular a gas-permeable plastic film,in particular a web of synthetic fibers such as polypropylene fibers(PP) or a Tyvek® protective film, which enables a sterilization of thecartridges accommodated therein through the film 6.

As will become apparent to a person skilled in the art, the bottom sideof the transport or packaging container (tub) 3 may also be formed open,e.g. in the manner of the tub 3 shown in FIG. 9, i.e. in the manner thatalso the bottom side of the tub is provided with a flange-like bottomrim in the manner of the upper rim 34 so that the bottoms of thecartridges 5 may be freely accessible for processing steps also from theunderside of the tub 3 if required.

As shown in FIGS. 1 and 2, for enabling an easy insertion of nest 1 intotub 3 and removal from the latter, access apertures 22 are formed on twolongitudinal sides of the supporting plate 10, via which gripping armsor the like may grab nest 22. As shown in FIG. 1, the access apertures22 are partially surrounded by upright side-walls 23 to prevent acollision of the gripping arms or the like with the cartridgesaccommodated. As shown in FIG. 1, the access apertures 22 are displacedrelative to each other, e.g. by one row, which further facilitates anunambiguous positioning of nest 1 in tub 3.

A packaging unit as shown in FIG. 9 accommodating presterilizedprefillable cartridges or syringe barrels can be stored under save andsterile conditions and then supplied to pharmaceutical customers forfurther processing. Particularly, the pharmaceutical customers will thenfill medicine or other liquids into the presterilized nested syringebarrels via the filling openings using conventional filling andstoppering machines, which may be any of the three following types offilling and stoppering machines: 1) manual machines, 2) semi automaticmachines and 3) fully automatic machines.

An example of such a filling operation is shown in FIG. 11 in aschematic cross-sectional view. At the time of delivery under sterileconditions, the packaging unit will be sealed by a lid or protectivefoil as outlined above (not shown), while the nest 1 will be supportedon the supporting step 32 of tub 3. At the time of delivery understerile conditions, the packaging unit may be packages further in atleast one sterile plastic bag. The cartridges 5, which are sealed byseals 55, e.g. pre-crimped, at their bottom ends will be accommodatedupside-down in the receptacles of nest 1 so that their filling openings53 face toward the upper end of tub 3 and the lid or protective foil(not shown). The height level of the upper ends of cartridges 5 is thusprecisely defined in relation to the level of the supporting plate 10,which is essentially equal to the level of supporting step 32 of tub 3,because the supporting plate 10 rests directly on supporting step 32.

The exemplary filling process shown in FIG. 11 considers that thesupporting plate 10 rests directly on a rectangular holding frame 40after removal from tub 3. The inner free width of the holding frame 40,however, also allows for a direct support of the outer side ofsupporting step 32 on the holding frame. In either case the height levelof the upper ends of cartridges 5 is precisely defined in relation tothe level of the holding frame 40.

For performing the filling process, the holding frame 40 is transferredat a precisely defined height level to a filling station comprising arow of filling nozzles 41 supported by a holding arm 42 used forinjecting a liquid, e.g. a medicine, via the filling openings 53 intothe cartridges 5 supported by nest 1. Also the height level of thebottom ends of filling nozzles 41 is precisely defined so that anon-zero gap of well defined width Δz will be ensured between the upperends of the cartridges 5 and the bottom ends of filling nozzles 41.Usually, the width Δz of this gap will be precisely adjusted beforeperforming the process and will be part of the general settings of aprocessing station. The width Δz of this gap will be adjusted inaccordance with general safety regulations, in particular in accordancewith GMP (Good Manufacturing Practice) guidelines requirements.

For a given length of the cartridges 5 to be supported in a nest 1, theheight level of the upper ends of the cartridges 5 will be preciselydefined by the axial lengths of the receptacles 11 of nest 1 and thus bythe height level of the retaining protrusions 15. Thus, if differenttypes of cartridges 5 with different axial lengths are to be processedby one and the same processing station, according to the presentinvention no change of the general settings of the processing station isrequired. Rather, only a different type of nest 1 with receptacles 11 ofdifferent axial length needs to be used to thereby ensure that also thedifferent type of cartridge 5 will be fed to the processing station atthe same height level of the upper ends of the different type cartridges5.

As the different type of nest 1 required for the different type ofcartridge 5 together with the sealed cartridges 5 accommodated thereincan be inserted into the packaging unit in the same manner and as thewhole packaging unit can be sealed and transported under sterileconditions to the pharmaceutical customers, according to the presentinvention it can be ensured that also the different type of cartridgemay be processed under the same settings and conditions without the needof adjusting the general settings of the processing station.Furthermore, no additional hygienic permissions will be required forthis purpose. Thus, according to the present invention different typesof cartridges involving different axial lengths may be processed in thesame way and under the same general conditions and settings. Thus, thepresent invention enables a cost-efficient processing of presterilized,sealed cartridges.

As will become apparent to the person skilled in the art, the aboveprinciple of replacement of one type of nest by a different type forcompensating for different axial lengths of batches of different typesof cartridges also works for compensating for different outer diametersof batches of different types of cartridges. More specifically, if afirst batch of cartridges having a first outer diameter and a secondbatch of cartridges having a second outer diameter different to thefirst outer diameter needs to be processed by the same processingstation, according to the invention only a first type of nest used forthe first batch of cartridges and having receptacles of a diametercorresponding to the first outer diameter needs to be replaced by asecond type of nest to be used for the second batch of cartridges andhaving receptacles of a diameter corresponding to the second outerdiameter.

As will become apparent to the person skilled in the art upon studyingof the above, the afore-mentioned principle may also be applied ifaccess to the bottom ends of the cartridges is required, because alsothe height level of the bottom ends of all cartridges accommodated by anest is precisely defined in relation to the height level of the holdingframe 40. This even applies if the tub 3 should be supplied to thepharmaceutical customer with an open bottom sealed by a lid orprotective foil.

FIG. 12a shows a supporting structure for closures (in the followingnest for closures or closure nest) in a perspective bottom view, whichcomprises a planar supporting plate 60 having a plurality of tubularreceptacles 61 disposed in a regular arrangement, which at least extenddownward from the bottom side of the planar supporting plate 60, andpreferably also protrude upward from the upper side of the supportingplate 60, as shown in the sectional views of FIGS. 12d and 12e for afurther embodiment. Thus, the tubular receptacles 61 are formed by thecircumferential side-walls 62, 63 protruding from the upper and bottomside of the supporting plate 60, respectively. Preferably theseside-walls 62, 63 are of cylindrical shape for accommodating theclosures 200, although other shapes, such as elliptic shapes might alsobe possible. These receptacles 61 are disposed in the same regulartwo-dimensional arrangement as for the supporting structure forcartridges set forth above, at equidistant spacing.

FIG. 12c shows the insertion of a plurality of closures 200, such aselastic plugs or plunger stoppers, into the receptacles 61 of theclosure nest 2. For this purpose, the closures 200 are inserted fromabove or below into the receptacles 61 to a desired extent, preferablyuntil they are fully accommodated in the receptacles and the upper endsof the closures are at a minor distance to the upper ends of the upperside-walls 63 as defined by the retaining structures inside thereceptacles 61, as shown in FIG. 12 e.

For retaining the closures 200 reliably in the receptacles 61,particularly for avoiding that the closures 200 simply slide out of thereceptacles 61 during handling of the closure nest which might includereversing the orientation of the closure nest, the receptacles 61comprise retaining structures 66, 67 for releasably engaging with theclosures 200 for retaining the closures in the receptacles. Morespecifically, the retaining structures 66, 67 are formed on inner sidesof the circumferential side walls 62, 63 of the receptacles 61 andconfigured to cooperate with the closures in a form-fitting manner.

As shown in FIG. 12e , the retaining structures comprise protrusions 66,67 formed on the inner sides of the circumferential side walls 62, 63 ofthe receptacles. The protrusions 66, 67 may be formed as circumferentialprotrusions on the inner sides of the circumferential side walls 62, 63of the receptacles 61. Preferably, the protrusions 66, 67 are formed atequal angular distances along the inner sides of the circumferentialside walls 62, 63 of the receptacles 61.

At least one of the protrusions may be configured to mate to the outercontour of the closures 200 to be accommodated. As shown in FIG. 12e ,the closures 200 may have an undulated outer contour, having severalcircumferential concave recesses 202 or bulges 201, and the protrusionsmay be formed to at least partially mate this outer contour.

As shown in FIG. 12e , the receptacles 61 comprise upper retainingstructures 66 formed at an upper end of the receptacles 61 and bottomretaining structures 67 formed at a bottom end of the receptacles 61,wherein the distance between the respective upper and bottom retainingstructures is basically equal to the axial length of the closures 200 sothat the closures 200 may be retained loosely, i.e. even with radialand/or axial play, between the two retaining structures 66, 67, or atleast with minor friction only.

As shown in FIG. 12e , the upper retaining structures 66 are formed asconvexly curved protrusions protruding from the inner sides of the uppercircumferential side walls 63 of the receptacles 61, whereas the bottomretaining structures 67 are formed as hook-like protrusions protrudingfrom the inner sides of the lower circumferential side walls 62 of thereceptacles 61.

According to FIG. 12e , the bottom retaining structures 67 may bebeveled on an upper side thereof to support the bottom side of theclosures 200 thereon and reduce the forces required for pushing of theclosures 200 downward. According to FIG. 12e , the bottom retainingstructures 67 may also be beveled on a lower side thereof so that thereceptacles may rest directly and without inducing tension on the upperends of cartridges during stoppering, as shown in FIG. 15 and outlinedbelow in more detail.

For the transport, storage and packaging of a nest 2 as outlined abovetogether with the closures accommodated therein a transport or packagingcontainer 3 a (hereinafter also named tub for closures) is used asschematically shown in FIG. 13a . According to FIG. 13a , the transportor packaging container 3 a has basically the same configuration asdescribed above with reference to FIG. 7 and is essentially box-shapedor tub-shaped and has a base 30 a, a circumferential side wall 31 aprotruding essentially in vertical direction therefrom, a supportingstep 32 a protruding essentially rectangular therefrom, acircumferential upper side wall 33 a and an upper rim 34 a which isformed as a flange. The corners 35 a of the transport or packagingcontainer 3 a are suitably formed rounded, particularly near thesupporting step 32 a. Preferably, the upper side wall 33 a is formedinclined at a small angle of inclination with respect to a vertical tothe base 30 a in order to ease the insertion of the nest 2. Such atransport or packaging container 3 a is preferably formed from aplastics material, particularly by plastic injection molding, and ispreferably formed of a clear transparent plastic in order to enable avisual inspection of the nest 2 accommodated in the transport orpackaging container 3 a and of the closures accommodated in it. Therounded corners 64 of the supporting plate 60 mate to the inner roundedcorners 36 a of the tub 3 a, at least if disposed at the bottom end ofthe upper side walls 33 a.

As shown in FIG. 13a a plurality of nets 2 for closures can beaccommodated inside the same transport or packaging container 3 astacked one above the other. In the stacked configuration, the lowerends of the side-walls of an upper of two adjacent supporting plates 60may rest directly on the upper surface of the lower of two adjacentsupporting plates 60. Because the outer diameter of the receptacles 61(see FIG. 12e ) is larger than the inner diameter of the receptacles 61,the side-walls 64 will not penetrate into the upper ends 65 of thereceptacles 61. Thus, no spacers are required between adjacentsupporting plates, which contributes to optimizing the packing density.

FIG. 13b shows the tub and nest assembly 4 a with all nests insertedinto the tub 31 a for closures. For reasons of clarity, the closures areomitted in FIGS. 13a and 13 b.

FIG. 13c shows a further stage of sealing the tub and nest assembly 4 aof FIG. 13b , by sealing the upper end of tub 3 a with a protective foil6, which may be bonded to the circumferential flange 34 a and may begas-impermeable. Preferably, however, the protective foil 6 is agas-permeable plastic film, in particular a web of synthetic fibers suchas polypropylene fibers (PP) or a Tyvek® protective film, which enablesa sterilization of the interior of the transport or packaging container4 a by a flow of a sterilizing gas through the protective foil 6.

FIG. 13d shows the tub and nest assembly 4 a of FIG. 13c sterile sealedagainst the environment. In this condition the closures may be storedand transported under sterile conditions. For this purpose, the tub andnest assembly 4 a may be packaged additionally in at least onegas-impermeable plastic bag.

Referring to FIGS. 14a to 14g , a general setup for closing (stoppering)cartridges according to the present invention will be described.

For supporting and aligning a supporting plate 10 of a cartridge nest ina predetermined position and orientation, a bottom holding frame 80 isused, which comprises a central opening 84, whose contour correspondsexactly to the outer counter of the cartridge nest.

More specifically, as shown in FIG. 1 the receptacles 11 of thecartridge nest 1 are aligned in rows along a first direction, but arenot aligned in rows in a second direction perpendicular to this firstdirection. Instead, in the second direction each second receptacle 11 isoffset e.g. by half a distance between two adjacent receptacles 11 inthe first direction. The side-walls 12 of the receptacles 11 thus definean undulated contour along the second direction, i.e. in FIG. 1 alongthe left-hand and right-hand edge of supporting plate 10. Two oppositeedges of the central opening 84 of the bottom holding frame 80 exactlycorrespond to this undulating pattern, so that the cartridge nest 1 canonly be inserted in a given orientation that is unambiguously defined bythe undulating pattern formed by the receptacles 11 of the cartridgenest 1. By means of the bottom holding frame 80 the upper ends of thecartridges 5 are positioned at a precisely defined height level relativeto the machine holding frame 70, which may be part of a processingmachine for the processing of containers and may be provided in acleanroom or under sterile conditions, e.g. at a pharmaceutical companyor filler.

As shown in FIG. 14a , several spacer rods 72 are disposed on themachine holding frame 70 for precisely defining the position andorientation of the bottom holding frame 80. For this purpose, alignmenttips may be provided at the front ends of the spacer rods 72 that engagewith the alignment holes 81 formed in the bottom holding frame 80.

FIG. 14b shows how the cartridge nest is accommodated and positioned inthe opening of the bottom holding frame 80.

As shown in FIGS. 14a and 14c , several spacer rods 82 are disposed onthe upper side of bottom holding frame 80 for precisely defining theposition and orientation of an upper holding frame 90 used forpositioning and aligning a closure nest above and relative to theunderneath cartridge nest. Alignment tips 83 are provided at the frontends of the spacer rods 82 that engage with the alignment holes 91formed in the upper holding frame 90.

FIG. 14d shows how the upper holding frame 90 is positioned and alignedon the bottom holding frame 80. A plurality of openings or receptacles92 formed as through holes are formed in the upper holding frame 90 inexactly the same geometric arrangement as the receptacles of theunderneath cartridge nest.

FIG. 14e shows how the supporting plate 60 of a closure nest is put ontothe upper holding frame 90. For reasons of clarity the closures areomitted in FIGS. 14a-14g . As shown in FIG. 14e the supporting plate 60of the closure nest is put onto the upper holding frame 90 in such amanner that the side-walls of the receptacles on the bottom side of thesupporting plate 60 enter the openings or receptacles 92 of the upperholding frame 90 and are finally fully accommodated therein. Again, thiscan only be accomplished in a unique orientation and positioning that isunambiguously defined by the pattern formed by the openings orreceptacles 92 of the upper holding frame 90.

Thus, in the condition of FIG. 14f all receptacles 61 of the supportingplate 60 of the closure nest are precisely aligned with all receptaclesformed by the side-walls 14 of the cartridge nest and thus with allcartridges supported by the cartridge nest. FIG. 14g shows thisexemplary set-up in a perspective exploded view.

FIG. 15 shows the set-up of FIG. 14f in a schematic sectional view. Thisset-up may be accomplished in a stoppering machine or in a combinedfilling and stoppering machine, in which case the bottom holding frame80 could be identical with the holding frame 40 shown in FIG. 11 and thewhole set-up will be disposed under reduced pressure or vacuumconditions at least while performing the stoppering process.

As shown in FIG. 15, the bottom ends of the side-walls 62 of thereceptacles of the closure nest are precisely retained at the same levelby hook-like protrusions 94 formed at the lower ends of the cylindricalside-walls 93 of the receptacles of the upper holding frame 90. Morespecifically, the lower ends of the side-walls 62 of the receptacles ofthe closure nest rest on the upper sides of the hook-like protrusions94. As the upper holding frame 90, which is preferably made of a stablemetal sheet, has a high mechanical stability and stiffness and will notflex during the stoppering process, the above alignment of the closures200 with the underneath cartridges 5 will be maintained during allstages of the stoppering process.

As shown in FIG. 15, the lower ends of the cylindrical side-walls 93 ofthe receptacles of the upper holding frame 90 are beveled inwards sothat they can snuggle to the open upper ends of the cartridges 5, ifrequired. These lower ends may be coated with a resin or plastic toreduce tension in this region. During the stoppering process, preferablya very narrow gap exists between the upper ends of the cartridges 5 andthe lower ends of the cylindrical side-walls 93 of the receptacles ofthe upper holding frame 90.

As shown in FIG. 15, the inner diameter of the receptacles of theclosure nest corresponds to the inner diameter of the cartridges 5. Forclosing the upper ends of the cartridges 5, the closures 200 are pusheddownward out of the receptacles of the closure nest and into the fillingopenings at the upper ends of the cartridges 5, while the cartridges areaccommodated in the receptacles of the cartridge nest. The closures arepushed down by means of a plurality of adjustable pushing rods 121 ofthe stoppering machine 120. This stoppering process may be performedrow-wise but can also be performed simultaneously for all closures 200and cartridges 5 held by the nests. For this purpose, both the holdingplate 10 of the cartridge nest and the holding plate 60 of stopper nestare sufficiently stiff to ensure the above precise alignment of theclosures 200 and cartridges 5 at all stages of the stoppering process.

FIG. 10 shows in a schematic top view an example of a processingapparatus or station for performing a process according to the presentinvention, as outlined above, under sterile conditions. The processingapparatus 100 has a sterile inner volume 101 with an infeed section atthe left-hand side and an outfeed section at the right-hand sidethereof. For processing, sterile packaging units as outlined above arefed, via the infeed section, into the sterile inner volume 101. Duringthis infeed step the lids or protective foils of the packaging units areremoved so that the tub and nest assemblies accommodating thepresterilized cartridges and presterilized closures finally are disposednear the infeed position indicated by reference numeral 102. Forprocessing, the tub and nest assemblies are conveyed by a conveyer 106along the direction of the arrow shown in FIG. 10 until finally reachingthe outfeed position indicated by reference numeral 103. For conveyingthe nests either the nests are accommodated by holdings frames 40 orsimilar holding tables or the tubs respectively accommodating a nest areaccommodated by holdings frames 40 or similar holding tables. In anycase, the upper ends of the cartridges are fed to the processingstations 101 at precisely defined height levels.

The infeed and outfeed sections for the cartridges nests and the closurenests might be at different positions and particularly might be disposedat different height levels.

As an example for a process step, FIG. 10 shows the filling andstoppering of the cartridges accommodated by nests in the holding frames40. For the filling and stoppering, the nests or tub and nest assembliesfor cartridges and for closures are first conveyed to the waitingposition 104 and then to the filling and stoppering station 110, wherethe filling and stoppering process is usually performed row-wise, butmay also be performed simultaneously for all cartridges and closures.After filling and stoppering the nests holding the filled and stopperedcartridges or the tub and nest assemblies accommodating the filled andstoppered cartridges are finally conveyed to the outfeed positionindicated by reference numeral 103.

During stoppering of the cartridges, when usually large axial forceswill be exerted from above onto the cartridges, the symmetricarrangement of the retaining protrusions 15 (see FIG. 2) together withthat of the axial ribs 13 ensures a symmetric distribution of suchforces with only minor deformation of the general shape of thereceptacles 11 and of the retaining protrusions 15 so that both theprecise centering and the height levels of the cartridges will bemaintained.

Besides filling the sealed cartridges via the filling openings at theupper ends and/or stoppering the sealed cartridges at their upper endsusing rubber stoppers, the above procedure may equally be performed forpre gassing or post gassing the cartridges. As can be concluded fromFIGS. 2 and 4, the gaps formed between the axial ribs 13 of thereceptacles together with the gaps 16 between the retaining protrusions15 of the receptacles and the access apertures 22 further support aproper gas flow for pre gassing or post gassing of the cartridges whenthe nest is accommodated in a tub, because a sterilizing gas may flowessentially unhindered from the upper side of the nest towards thebottom side of the nest, if accommodated in a tub.

It will be appreciated that according to the present invention thesealed, particularly pre-crimped, cartridge barrels are entirely of aknown form and require no modification as compared to conventionalsealed cartridge barrels. Equally the tub is as currently employed in aknown prefillable syringe handling system and it is only the nest whichhas been modified in such a way that it will be interchangeable to aconventional nest of prefillable syringe nest in terms of height levelof sealed cartridge barrels in tub as well as on the filling machinetable or holding frame. Moreover, as the sealed cartridges allows to usethe same height setting of a prefillable syringe filling machine table,the down stand socket of the receptacles ensure that the sealedcartridge barrels are held at the same level of prefillable syringes ina conventional nest.

Thus, the supporting structure for cartridges according to the presentinvention may be used equally for a manual, semiautomatic orfully-automatic filling and stoppering process, as summarized below:

1) Manual Filling and Stoppering Machine for Prefillable Syringes

Normally this manual filling and stoppering machine as the name suggestsis used for filling and stoppering of prefillable syringes in anon-automated process. According to the present invention the customercan fill the medicine into other types of medical devices, i.e. intocartridges having a different axial length, while using the same fillingand stoppering machine because the nest and tub assembly according tothe present invention enables performing the same processing steps onsame machine without any change in filling machine parts and any changein machine setting.

Thus, keeping different change parts and different settings and also therequirement of separate validation studies can be avoided, whichotherwise will add on to the costs and also will require additional timeto change the parts resulting in production loss.

In case of a stoppering machine only the fixture top plate needs to bechanged to match the nest design if required without changing the heightof the fixture.

2) Semi-Automatic Filling and Stoppering Machine for PrefillableSyringes

Normally this semi-automatic filling and stoppering machine as the namesuggests is also used for filling and stoppering of prefillablesyringes. According to the present invention the customer can fill themedicine into other types of medical devices, i.e. into cartridgeshaving a different axial length, while using the same filling andstoppering machine because the nest and tub assembly according to thepresent invention enables performing the same processing steps on samemachine without any change in filling machine parts and any change inmachine setting, particularly without any change in the filling tableheight. The same advantages result as outlined above for manual Fillingand stoppering machines.

3) Fully-Automatic Filling and Stoppering Machine for PrefillableSyringes

The nested tub for sealed, particularly pre-crimped, presterilizedcartridges according to the present invention can be directly fed onexisting fully-automatic filling and stoppering machines of prefillablesyringes without any setting change in the machine and withoutadjustment or change in the filling table height and only by replacementof one change part i.e. carrier resting plate to match the nest designif required.

The following further advantages of the inventive nest for cartridgesexist:

-   1) The cartridge nest design is developed in such a way that the top    level of the cartridges in the tub and nest is maintained exactly at    the same top height as that of prefillable syringe in conventional    tub and nest format.-   2) Ribs are provided on the top and/or bottom surface of the nest    for maintaining the surface of the nest in horizontal position    without bending or cave in downwards towards the tub.-   3) The retaining protrusions of each socket have a flower type    profile (shown in FIGS. 3 and 4) to hold the sealed cartridges at    the shoulder portions. The bottom flower type profile is designed in    such a way that it can hold the cartridge stably throughout it's    processing, especially during stoppering operation where maximum    forces are applied on the nest bottom flower type profile. Bottom    flower type profile can sustain up to 1,000 N force.

While specific embodiments of the invention have been described indetail, it will be appreciated by those skilled in the art that variousmodifications and alternatives to those details could be developed inlight of the overall teachings of the disclosure. Accordingly, theparticular arrangements disclosed are meant to be illustrative only andnot limiting as to the scope of the invention which is to be given thefull breadth of the appended claims and any and all equivalents thereof.

LIST OF REFERENCE NUMERALS

-   1 supporting structure for cartridge (also named cartridge nest)-   2 supporting structure for cartridge stoppers (also named stopper    nest)-   3 transport or packaging container for cartridges (also named tub)-   3 a transport or packaging container for stoppers (also named tub)-   4 tub and nest assembly (for cartridges)-   4 a tub and nest assembly (for stoppers)-   5 cartridge-   6 sealing lid-   10 (planar) holding plate of cartridge nest 1-   11 receptacle-   12 side wall of receptacle 11 on upper side-   13 axial rib-   14 side wall of receptacle 11 on bottom side-   15 retaining protrusion-   16 gap between retaining protrusions 15-   17 central opening-   20 rounded corner-   21 extension-   22 gripping aperture-   23 side wall of gripping aperture 22-   24 guiding web-   25 guiding web-   26 stiffening web on upper side-   27 stiffening web on bottom side-   28 stiffening web on bottom side-   30 bottom (of tub for cartridges)-   30 a bottom (of tub for stoppers)-   31 lower side wall (of tub for cartridges)-   31 a lower side wall (of tub for stoppers)-   32 supporting step (of tub for cartridges)-   32 a supporting step (of tub for stoppers)-   33 upper side wall (of tub for cartridges)-   33 a upper side wall (of tub for stoppers)-   34 upper flange (of tub for cartridges)-   34 a upper flange (of tub for stoppers)-   35 rounded corner (of tub for cartridges)-   35 a rounded corner (of tub for stoppers)-   36 a inner rounded corner (of tub for stoppers)-   40 holding frame-   41 filling nozzle-   42 holding arm for filling array of nozzles 41-   43 holding arm for stoppering devices-   50 cylindrical body-   51 shoulder portion-   52 widened upper rim-   53 filling opening-   54 bottom opening-   55 seal-   60 supporting plate of stopper nest 2-   61 receptacle-   62 side wall of receptacle 61-   63 upper extension of side wall 62-   64 rounded corner-   65 upper end of receptacle 61-   66 upper fixing protrusion-   67 bottom retaining protrusion-   70 machine holding frame-   71 opening-   73 spacer rod-   80 bottom holding frame-   81 alignment hole-   82 spacer rod-   83 alignment tip of spacer rod 82-   84 opening of central holding frame 80-   90 upper holding frame-   91 alignment hole-   92 receptacle-   93 cylindrical side wall-   94 bottom protrusion-   100 processing apparatus-   101 sterile inner volume-   102 tub and nest assembly at infeed-   103 tub and nest assembly at outfeed-   104 nest assembly at waiting position-   105 nest assembly at filling station-   106 conveyor-   110 process station for filling and stoppering-   111 downstream processing station-   120 stoppering machine-   121 pushing rod-   200 stopper-   201 protrusion-   202 recess

1. A method for closing a plurality of pre-crimped cartridges for use inpharmaceutical, medical or cosmetic applications, said pre-crimpedcartridges having an upper end and a bottom end opposite to the upperend, a cylindrical body with a filling opening at the upper end, and ashoulder portion at the upper end, which is followed by a widened upperrim with a secondary opening for drug administering, wherein thesecondary opening is sealed by a seal and an outer closure is crimpedover the widened upper rim to secure the seal at the pre-crimpledcartridge, said method comprising: providing a supporting structure forclosures having a plurality of tubular receptacles disposed in a regulararrangement, wherein the receptacles releasably accommodate a pluralityof closures at least partially and comprise retaining structures forreleasably engaging with the closures for retaining the closures in thereceptacles; providing a supporting structure for cartridges having aplurality of tubular receptacles disposed in the same regulararrangement, which are formed by circumferential side-walls protrudingfrom a supporting plate of the supporting structure for cartridges andwhich accommodate a plurality of pre-crimped cartridges, whereinretaining protrusions are formed at the bottom ends of the receptaclesprotruding inward and the pre-crimped cartridges are accommodatedupside-down in the receptacles so that the shoulder portions of thepre-crimped cartridges are supported on the retaining protrusions of thereceptacles and the sealed upper ends of the pre-crimped cartridgesextend through central openings formed by the retaining protrusions atthe bottom ends of the receptacles; disposing the supporting structurefor closures above the supporting structure for cartridges in anenvironment with reduced pressure so that the receptacles of thesupporting structure for closures are aligned with the receptacles ofthe supporting structure for cartridges; and pushing the closuresdownward out of the receptacles of the supporting structure for closuresand into the filling openings at the bottom ends of the pre-crimpedcartridges, while the pre-crimped cartridges are accommodated in thereceptacles of the supporting structure for cartridges.
 2. The method asclaimed in claim 1, wherein the supporting structure for cartridges isheld by a bottom holding frame; the supporting structure for closures isheld by an upper holding frame above the bottom holding frame; and thebottom holding frame and the upper holding frame are disposed at a fixedspacing and aligned with each other by alignment devices.
 3. The methodas claimed in claim 2, wherein the upper holding frame is disposed atsuch a distance to the bottom holding frame that bottom ends ofreceptacles of the upper holding frame (90) or bottom ends of thereceptacles of the supporting structure for closures held by the upperholding frame are in direct contact with or at a small distance to thebottom ends of the pre-crimped cartridges accommodated in thereceptacles of the supporting structure for cartridges.
 4. The method asclaimed in claim 1, wherein the step of providing the supportingstructure for closures further comprises: providing a transport orpackaging container accommodating a plurality of supporting structuresfor closures which is sterile sealed against the environment by aprotective foil bonded on a circumferential flange of the transport orpackaging container; removing the protective foil from thecircumferential flange to thereby open the transport or packagingcontainer; and removing one of the supporting structures for closuresout of the transport or packaging container.
 5. The method as claimed inclaim 4, wherein the transport or packaging container accommodating theplurality of supporting structures for closures is box-shaped andcomprises: a bottom, which is closed or sealed by a seal, upstandinglower side-walls extending essentially perpendicularly from said bottom,a circumferential supporting step extending horizontally from saidside-walls, upper side-walls extending upward from said supporting step,and the circumferential flange formed at upper ends of the upperside-walls, wherein the bottommost supporting structure for closures issupported on the circumferential supporting step, and the plurality ofsupporting structures for closures are accommodated inside the transportor packaging container stacked one above the other.
 6. The method asclaimed in claim 1, wherein the step of providing the supportingstructure for cartridges further comprises: providing a transport orpackaging container accommodating the supporting structure forcartridges, which is sterile sealed against the environment by aprotective foil bonded on a circumferential flange of the transport orpackaging container; removing the protective foil from thecircumferential flange of the transport or packaging container tothereby open the transport or packaging container accommodating thesupporting structure for cartridges; and removing the supportingstructure for cartridges out of the transport or packaging container. 7.The method as claimed in claim 6, wherein the transport or packagingcontainer for accommodating the supporting structure for cartridges isbox-shaped and comprises: a bottom, which is closed or sealed by a seal,upstanding lower side-walls extending essentially perpendicularly fromsaid bottom, a circumferential supporting step extending horizontallyfrom said side-walls, upper side-walls extending upward from saidsupporting step, and the circumferential flange formed at upper ends ofthe upper side-walls, wherein the supporting structure for cartridges issupported on the circumferential supporting step, the bottom ends of thepre-crimped cartridges are disposed at the same height level but do notprotrude beyond the circumferential flange of the transport or packagingcontainer for accommodating the supporting structure for cartridges, andthe upper ends of the pre-crimped cartridges are disposed spaced apartfrom the bottom of the transport or packaging container foraccommodating the supporting structure for cartridges.
 8. The method asclaimed in claim 1, further comprising a step of filling a plurality ofthe pre-crimped cartridges with a pharmaceutical, medical or cosmeticproduct.
 9. The method as claimed in claim 8, wherein the step offilling the plurality of pre-crimped cartridges with the pharmaceutical,medical or cosmetic product comprises filling the plurality ofpre-crimped cartridges with the pharmaceutical, medical or cosmeticproduct simultaneously while the pre-crimped cartridges are supported bythe supporting structure for cartridges.
 10. The method as claimed inclaim 9, wherein the step of filling the plurality of pre-crimpedcartridges with the pharmaceutical, medical or cosmetic product isperformed while the supporting structure for cartridges is held in abottom holding frame.
 11. A supporting structure for releasablysupporting a plurality of closures for closing cartridges for use inpharmaceutical, medical or cosmetic applications, said closures having acylindrical shape and consisting of a resilient material, saidsupporting structure comprising a planar supporting plate having aplurality of tubular receptacles for completely accommodating theclosures for concurrently supporting a plurality of closures at thesupporting plate, wherein the receptacles are formed by circumferentialside walls disposed in a regular arrangement at the supporting plate andprotruding from the supporting plate, the receptacles are configured foraccommodating the closures completely, and the receptacles compriseupper retaining structures formed at or near an upper end of thereceptacles and bottom retaining structures formed at a bottom end ofthe receptacles, for releasably engaging with the closures for retainingthe closures in the receptacles, wherein the upper retaining structuresare formed as convexly curved protrusions protruding from the innersides of the circumferential side walls of the receptacles, the bottomretaining structures are formed as hook-like protrusions protruding fromthe inner sides of the circumferential side walls of the receptacles,and the bottom retaining structures are beveled on an upper and/or lowerside thereof.
 12. The supporting structure as claimed in claim 11,wherein the retaining structures (66, 67) are formed on inner sides ofthe circumferential side walls of the receptacles.
 13. The supportingstructure as claimed in claim 12, wherein the retaining structurescomprise protrusions formed on the inner sides of the circumferentialside walls of the receptacles.
 14. The supporting structure as claimedin claim 13, wherein the protrusions are configured to mate to the outercontour of the closures.
 15. The supporting structure as claimed inclaim 13, wherein the protrusions are formed at equal angular distancesalong the inner sides of the circumferential side walls of thereceptacles.
 16. The supporting structure as claimed in claim 13,wherein the protrusions are formed as circumferential protrusions on theinner sides of the circumferential side walls of the receptacles. 17.The supporting structure as claimed in claim 11, wherein the distancebetween the respective upper and bottom retaining structures is smallerthan or equal to the axial length of the closures.
 18. (canceled) 19.(canceled)
 20. A transport or packaging container for accommodating aplurality of closures for closing cartridges for use in pharmaceutical,medical or cosmetic applications, wherein the transport or packagingcontainer is box-shaped and comprises: a bottom, which is closed orsealed by a seal, upstanding lower side-walls extending essentiallyperpendicularly from said bottom, a circumferential supporting stepextending horizontally from said side-walls, upper side-walls extendingupward from said supporting step, and a circumferential flange formed atupper ends of the upper side-walls; and a plurality of supportingstructures for closures as claimed in claim 11 is accommodated in thetransport or packaging container; wherein the plurality of closures areaccommodated in the receptacles of the at least one supporting structurefor closures.
 21. The transport or packaging container as claimed inclaim 20, wherein the edge of the bottommost planar supporting plate ofthe plurality of supporting structures for closures accommodated in thetransport or packaging container is supported on the circumferentialsupporting step or the transport or packaging container.
 22. (canceled)23. The transport or packaging container as claimed in claim 20, whereinthe transport or packaging container is closed or sealed by a protectivefoil against the environment, the protective foil being bonded to thecircumferential flange.
 24. The transport or packaging container asclaimed in claim 23, wherein the protective foil is a gas-permeableplastic film, in particular a web of synthetic fibers such aspolypropylene fibers (PP) or a Tyvek® protective film, which enables asterilization of the interior of the transport or packaging containerthrough the protective foil.